Table 1.
Immunogenicity and safety data from pivotal phase II/III studies for novel recombinant B-MD vaccines.
| Author, vaccine, study design | Immunogenicity | Safety | Concomitant vaccines |
|---|---|---|---|
| Gossger N, et al. 4CMenB53 | After priming ≥ 99% reached protective titers (hSBA ≥ 5) against Nad A, fHbp; and 79 – 86,1% for PorA tests strains. | Fever was more frequent after 4CMenBdoses (26%-41%) compared with routine vaccines (23%-36%); severe erythema, swelling, or induration were seen in ≤ 1%; severe pain was registered in 16% in the accelerated groups. | PCV7 and DTaP-HBV-IPV/Hib |
| Phase IIb, multicenter, open-label, parallel group, randomized controlled trial; infants 2 months of age including two different 3 +1 schedules (sole or co-administered with routine vaccines); N = 1,885 | Immune responses were non-inferior by concomitant vaccination; and its immunogenicity was non-inferior to routine vaccines alone for all antigens. | No evidence of immune interference, except for pertactin and pneumococcal serotype 6B, of unlikely clinical significance. | |
| Sole administration elicited higher hSBA GMTs for all strains compared to coadministration with routine vaccines; 2,4, and 6-month schedule, rather than an accelerated 2-, 3-, and 4-month schedule, resulted in higher hSBA GMTs for the Nad A test strain. | Increase in reactogenicity in the coadministration group, mainly fever (51%-61%) and severe pain at the injection site (12%). | ||
| Vesikari T, et al, 4CMenB52 | After priming 100% reached hSBA ≥ 5 against fHbp and Nad A, and 84% for New Zealand OMV and NHBA tests strains. | Fever, injection-site reactions and tenderness were the most frequent adverse events reported | PCV7 and DTaP-HBV-IPV/Hib; MMRV |
| Phase III, multicenter, randomized, open label for immunogenicity and observer blind for safety; infants 2 – 12 months of age; 3 +1 schedule | After booster dose: 95−100% of children had hSBA ≥ 5 for all antigens. | Fever: usually on day 1, returning to normal by day 3. | No evidence of immune interference, except for poliovirus type 2 responses, with unknown clinical significance. |
| N = 3,360 | Injection-site reactions: peaked on day 1, with a steep decrease on day 2 and lower incidence after booster. | Increase in reactogenicity in the coadministration group; mainly fever (77% vs. 45%). | |
| Martinón-Torres F, et al, 4CMenB50 | After priming for groups 1 to 3, and after the catch up series for group 4 100% and 99% reached hSBA ≥ 4 against fHbp and Nad A; | In infants local tenderness, erythema and pain were the most commonly reported adverse effects | None |
| Phase IIIb, multicenter, randomized, open-label; healthy subjects from 2 ½ months to 10 years old, divided in four groups: | After primary/catch-up series hSBA ≥ 4 against Por A was reached in groups 1,3 and 4 in 99% and in 98% for group 2. | Rates of systemic adverse reactions in infants were similar across the 3 groups and highest after the first vaccination. Across all groups, no increased reactogenicity was observed following subsequent vaccinations | |
| Group 1: doses at 2½, 3½, and 5 + 11 months of age; | NHBA 1 month after primary/catch-up series reached 59% for group 1, 49% for group 2, 77% for group 3, and 95% for group 4 | ||
| Group 2: doses at 3½ and 5 + 11 months of age; | After booster response (measured in groups 1,2 and 3) 100% reached hSBA titers ≥ 4 for fHbp and Nad A, ≥99% for Por A | ||
| Group 3: dose at 6 and 8 + 11 months of age. | NHBA reached hSBA titers > 4 in 84%, 88% and 87% in groups 1, 2 and 3 respectively. | ||
| Group 4: 2-dose-catch-up series, administered 2 months apart. | |||
| N = 754 infants and 404 children | |||
| Santolaya ME, et al., 4CMenB54 | After 1 dose: 92–97% had hSBA titers ≥ 4 against test strains | Local and systemic reaction rates were similar after each injection and did not increase with subsequent doses, but remained higher than placebo. | None |
| Phase IIb/III, multicenter, randomized, observer-blind, placebo-controlled study; adolescents from 11 to 17 years old; 1, 2 or 3 dosing schedule with 1,2 and/or 6 month intervals; N = 1,631 | After 2 or 3 doses: 99–100% had hSBA titers ≥ 4 against test strains; reaching seroresponse rates of 99–100% for each strain at 6 months. | Pain was reported in 86% of which 17% was severe, most resolving at day 3; malaise: 51%; headache: 42% and fever: 4%; all the above were statistically significant compared to placebo. | |
| A third dose had a small incremental effect on geometric mean titers, especially when given at 6 months, but did not increase the proportion of participants achieving protective titers | No vaccine-related SAEs were reported and no significant safety signals were identified. | ||
| Vesikari T, el al. rLP208663 | Participants whom elicited hSBA titers ≥1: 8 for serogroup B test strains expressing vaccine-heterologous fHbp variants A22, A56, B24, and B44: After 2 doses: 90–93%, 98–100%, 69–81%, and 70–77%. | Pain at the injection site, redness and swelling were the most common reactions and were mild to moderate. Severe pain was reported by 9.9% of subjects | None |
| Phase II, randomized, multicenter, single-blind study; adolescents from 11 – <19 years old; 2- or 3-dose schedules (0,1,6-month; 0,2,6-month; 0,2-month; 0,4-month; 0,6-month); N = 1,713 | After 3 doses: 92–95%, 98–99%, 88–89%, and 86–88%. | Headache and fatigue were the most common systemic symptoms and were mild or moderate in severity. Fever was infrequent (1.7%–4.3%). | |
| GMTs were similar between the 2- and 3-dose regimens. | There were no differences in the incidence of SAEs between bivalent rLP2086 and saline recipients. | ||
| Muse D, et al.; rLP208664 | Immune responses to MCV4 + Tdap + rLP2086 were non-inferior to MCV4 + Tdap or rLP2086 alone. Seroprotective hSBA (>1:4) were documented for 62.3%–68.0% and 87.5%–90% of MCV4 + Tdap + bivalent rLP2086 recipients after doses 2 and 3, respectively. A ≥4-fold rise in hSBA titers from baseline was achieved by 56.3% – 64.3% and 84.0%–85.7% of subjects after doses 2 and 3, respectively. Bivalent rLP2086 alone induced similar responses. | Concomitant administration did not substantially increase reactogenicity compared with rLP2086 alone. | MCV4 and Tdap |
| Phase II, multicenter, randomized, active-controlled, observer-blinded study; adolescents from 10 to <13 years old; concomitant or standalone schedule: 0,2 and 6 months; N = 2,648 | Bivalent rLP2086 concomitantly with MCV4 + Tdap met all noninferiority immunogenicity criteria without an increase in reactogenicity. | ||
| Ostergaard L, et al.; rLP208667 | Immunogenicity data were not collected | SAEs: 1.6% of rLP2086 recipients | None |
| Phase III, multicenter, randomized, active-controlled, observer-blind study; adolescents and young adults ≥ 10 – <26 years old; 3 doses schedule (0, 2, and 6 months); N = 5,712 | Medically attended AEs were similar between rLP2086 and hepatitis A vaccine/placebo group (5,5% – 7%) and decreased after each consecutive dosing | ||
| Subjects reporting ≥ 1 AE were greater in the rLP2086 vaccine group. | |||
| Ostergaard L, et al.; rLP208668 | After 2 doses hSBA titer ≥ 4 against each primary strain ranged from 56.0 to 85.3% in subjects 10 – 18 years old and from 78.8 to 90.2% after dose 3 | Pain was the most common reaction in the two trial groups, mainly after dose 1, and ≤1.1% reported increased severity of reaction with subsequent doses | None |
| Phase III, multicenter, randomized, controlled, observer-blinded, adolescents from 10 – 18 years old and from 18 to 25 years old; 3 doses (0,2 and 6 months) | Young adults with hSBA titers ≥ 4 ranged from 54.6 to 85.6% and 78.9 to 89.7%, after doses 2 and 3, respectively | Headache and fatigue were the most common systemic events among both adolescents and young adults | |
| N = 3596 adolescents (10 to 18 years of age); 3304 young adults (18 to 25 years of age) | Composite responses after doses 2 and 3 in adolescents were 53.7% and 82.7%, respectively, and those in young adults were 63.3% and 84.5%, respectively |
4CB-MD: Bexsero®; fHbp: factor H binding protein; Nad A: neisserial adhesin A; neisseria heparin binding antigen: NHBA; OMV: outer-membrane vesicle; hSBA: human complement serum bactericidal activity; GMTs: geometric mean titres; SAE: serious adverse events; AE: adverse event; SBA: serum bactericidal assays; hSBA: serum bactericidal assays using human complement; PCV7: heptavalent pneumococcal conjugate vaccine; DTaP-HBV-IPV/Hib: diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, inactivated poliomyelitis, hepatitis B vaccine; MMRV: measles, mumps, rubella, varicella; MCV4: meningococcal ACWY conjugate vaccine; Tdap: tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed.